tbuckley/cabot-search huggingface dataset:
Intra- and peri-tumoral radiomics based on dynamic contrast-enhanced MRI for prediction of benign disease in BI-RADS 4 breast lesions: A multicentre study.
Authors: Yalan Hu, Zhenhai Cai, NiJiati AiErken, Yueqi Liu, Nan Shao, Zhen Shan, Xiaoling Zhang, Ying Lin
Journal: Journal of Clinical Oncology (2023)

e13542 Background: The study aimed to develop and optimize a radiomics model with features extracted from breast intra- and peri-tumoral region in dynamic contrast-enhanced (DCE) MRI to distinguish benign from malignant breast lesions of Breast Imaging Reporting and Data System (BI-RADS) 4, thereby obviating unnecessary biopsies. Methods: We retrospectively analyzed data of women with BI-RADS 4 or 5 lesions from three hospitals. The regions of interest (ROIs) of intra-tumoral regions were delineated manually on each slice of image. The peri-tumoral regions were then obtained by equidistant 3-dimensinal dilation of the tumor border with 1, 2 and 3mm, respectively. Seven classification models were built with features extracted from the intra- and peri-tumoral regions, including the Intra, Peri1mm, Peri2mm, Peri3mm, Intra+peri1mm, Intra+peri2mm and Intra+peri3mm. Diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUC) and compared by DeLong test. Subgroup analysis was performed after stratifying all lesions by enhancement pattern. To assess the rate of avoidable biopsies, three exploratory cutoff values on the ROC curve were examined. Results: The Comb2 model, built with features from peri-tumoral 2mm and intra-tumoral region, demonstrated the best performance with AUCs of 0·901 and 0·863 in the development and external test cohort, respectively. The Comb2 model was robust in both mass and non-mass enhancement lesions. At the three exploratory cutoff values on the ROC curve, the model identified 11·2% (sensitivity of C1≥90%), 49·5% (sensitivity of C2≥95%) and 63·3% (sensitivity of C3≥98%) of the benign lesions in the development cohort. Applying the identified cutoff values in the external test cohort showed the potential to lower the number of unnecessary biopsies of benign lesions. Conclusions: An MRI-based radiomics model built with features extracted from the intra-tumoral region combined with the peri-tumoral 2mm showed the best potential to reduce false-positive diagnoses and may avoid unnecessary biopsies with a low underestimate risk.
Phase II neoadjuvant trial of albumin-bound paclitaxel, trastuzumab and pertuzumab followed by anthracycline based regimens in patients with operable HER2 positive breast cancer (OMC-BC05).
Authors: Mitsuhiko Iwamoto, Ayana Ikari, Tomo Tominaga, Saki Maezawa, Junna Sakane, Hiroyo Oku, Katsuhide Yoshidome, Takashi Morimoto, Hiroya Fujioka, Seita Hagihara, Toshikatsu Nitta, Ayumi Matsutani, Kosei Kimura
Journal: Journal of Clinical Oncology (2023)

e12594 Background: Anthracycline and Taxane have been widely used and studied in neoadjuvant setting for treatment of locally advanced breast cancer. Various regimens have explored the addition of newer agents to determine safety and efficacy, and pathological complete response(pCR) has been demonstrated to be associated with favorable overall survival in primary breast cancer. Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to Trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (Her2)-positive breast cancer. In addition, APHINITY trial showed that Pertuzumab significantly improved the rates of invasive-disease-free survival among patients with HER2-positive, operable breast cancer when it was added to Tastuzumab and chemotherapy. We conducted a clinical phase II neoadjuvant trial of nab-Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline Based Regimens in Patients with Operable Her2 Positive Breast Cancer. Methods: The study is designed to evaluate nab-paclitaxel, Trastuzumab and Pertuzumab followed by EC or AC or FEC as neoadjuvant therapy in patients with Her2 positive operable breast cancer. Patients are treated with neoadjuvant nab-paclitaxel(260 mg/m 2 ), Trastuzumab and Pertuzumab followed by EC(Epirubicin 90 mg/m 2 , Cyclophosphamide 600 mg/m 2 ) or AC(Doxorubicin 60 mg/m 2 , Cyclophosphamide 600 mg/m 2 ) or FEC(Fluorouracil 500mg/m 2 , Epirubicin 100 mg/m 2 , Cyclophosphamide 500 mg/m 2 ) q21d x 4. Patients undergo surgery 4-6 weeks later from completing chemotherapy. The primary endpoint, pCR is defined as no evidence of invasive tumors in the final surgical sample both in the breast and axillary lymph nodes. Secondary endpoints include overall response rate, disease-free survival, rate of breast conserving surgery, histological response rate, rate of sensory neuropathy ant the safety of the treatment. Results: In 30 evaluable patients, the pCR rate was 50%; 6/19 (31.6%) in ER-positive and 9/11 (81.8%) in ER-negative, 1/7 (14.3%) in IHC 2+, FISH positive and 14/23 (60.9%) in IHC 3+ . Of the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; no patient required a dose reduction for nab-PTX because of peripheral neuropathy. Conclusions: Neoadjuvant treatment using albumin-bound Paclitaxel, Trastuzumab and Pertuzumab followed by Anthracycline based regimens appears to be effective especially in pure HER2 type or IHC 3+ cases.
Clinical evidence and benefit of special FDA designations in anti-cancer drugs.
Authors: Daniel Tobias Michaeli, Julia Caroline Michaeli, Sebastian Albers, Tobias Boch, Boris Winterhoff, Thomas Michaeli
Journal: Journal of Clinical Oncology (2023)

e13655 Background: Over the past decades, US congress enabled the US Food and Drug Administration (FDA) to facilitate and expedite drug development for serious conditions filling unmet medical needs with five special designations: orphan, fast track, accelerated approval, priority review, and breakthrough therapy. It remains unclear whether multiple designations per indication are redundant. This study analyzes cancer drugs with multiple special designations regarding their FDA approval timelines, evidence, benefit, epidemiology and price. Methods: All anti-cancer drugs and their supplemental indication approvals were identified in the Drugs@FDA database from 2000 to 2022. For each indication, clinical trial characteristics, epidemiologic, and price data were collected from FDA labels, the Global Burden of Disease Study, and Medicare &amp; Medicaid Part B and D, respectively. The association between overall survival (OS) and progression-free survival (PFS) hazard ratios (HR) and drug indications’ number of special designations were compared in meta-analyses and meta-regressions. Results: We identified 170 anti-cancer drugs with FDA approval in 455 indications. The median time to first FDA approval was 13.8 years for drugs with zero, 7.3 years with one, 7.1 years with two, 7.8 with three, 5.8 with four, and 5.3 with five special designations (HR per additional designation: 1.27, 95%CI: 1.09-1.48, p=.002). Drug indications with more special designations were more frequently granted to rare diseases with fewer treatment options supported by smaller and shorter open-label phase 1/2 trials. OS HRs were 0.79 for indications with zero, 0.74 with one, 0.73 with two, 0.69 with three, 0.59 with four, and 0.52 with five special designations (p=.024). On average, each additional special designation was associated with lower HRs for OS (ß=-0.03, p=.002) and PFS (ß=-0.07, p&lt;.001). Each additional special designation was associated with a 19.05% (95%CI: 4.56-35.55, p=.013) higher drug price. Conclusions: The FDA’s special designations are non-redundant. Multiple special designations are associated with faster approval times and a greater efficacy for patients with high unmet needs, while multiple special designations are associated with less robust trial evidence and higher drug prices. This study supports the strategy of special FDA designations for unmet clinical needs.
CAPTOR-BC: Comprehensive analysis of spatial, temporal and molecular biomarkers predicting response and resistance to first-line treatment with ribociclib + ET in HR+, HER2- advanced breast cancer.
Authors: Peter A. Fasching, Sara Brucker, Hanna Huebner, Verena Thewes, Lea Louise Volmer, Andreas Daniel Hartkopf, Hans-Christian Kolberg, Benno Lex, Bahriye Aktas, Nina Ditsch, Lothar Haeberle, Katharina Seitz, Daniel Anetsberger, Naiba Nabieva, Christian Roos, Erik Belleville, Andreas Schneeweiss, Volkmar Mueller, Wolfgang Janni, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2023)

TPS1124 Background: The combination of an oral CDK4/6 inhibitor with endocrine therapy (ET) has become the standard first-line therapy for women with advanced HR+ HER2- breast cancer. In this context, the broadest clinical trial data are available for ribociclib, a highly selective CDK4/6 inhibitor, with three phase III trials (MONALEESA-2, -3 and -7) consistently showing a significant overall survival benefit compared to ET monotherapy regardless of treatment line, menopausal status or combination partner. However, de novo or acquired resistance to CDK4/6 inhibitors does occur and biomarkers predicting treatment response or providing information on resistance mechanisms are only beginning to be understood. Comprehensive identification and validation of biomarkers before and during ribociclib therapy is needed to better understand mechanisms leading to disease progression, which will be the first step towards developing novel therapies and optimizing treatment sequences. Methods: CAPTOR-BC (NCT054552213) is a single-arm, open-label phase IV study evaluating the combination of ribociclib and ET according to SmPC in the first-line treatment of HR+ HER2- advanced breast cancer to identify and validate molecular and non-molecular biomarkers predictive of drug response and resistance. First patient first visit occurred in October 2022 and at least 1000 patients across more than 75 sites in Germany will be enrolled until October 2025. Progression-free survival (PFS) and overall survival (OS) at 12 months are the co-primary endpoints, quality of life (QoL) and toxicity are secondary endpoints. Exploratively, a comprehensive multi-omics biomarker discovery and validation program is integrated into the study: Besides tumor tissue, liquid biopsies profiling circulating tumor (ct)DNA, ctRNA, whole blood RNA, proteins from serum and plasma, and circulating immune cells will be evaluated before, during and after treatment or upon progression to determine correlations with PFS, OS, QoL and adverse events. Clinical trial information: NCT05452213 .
Identifying determinants of pathologic complete response in patients with breast cancer after receiving neoadjuvant systemic therapy.
Authors: Abigail Sy Chan, Anika Bhargava, Natasha Chandler, Michelle Tavcar, Bakeerathan Gunaratnam, Brian Dong
Journal: Journal of Clinical Oncology (2023)

e12622 Background: In locally advanced breast cancer, neoadjuvant systemic therapy aims to downstage the disease, clear micrometastasis, assess chemosensitivity, and allow for breast conserving surgery. The attainment of a Pathologic Complete Response (pCR) has been associated with improved event free survival (EFS) and improved overall survival (OS) among various studies. We aim to identify clinicopathological factors which may influence pCR. Methods: This is a single center retrospective study of patients diagnosed with locally advanced breast cancer from 2017-2022 who received neoadjuvant therapy and investigating predictors of pCR in this subset of patients. Descriptive statistics were used to summarize the baseline characteristic variables. Variables relating to pCR were analyzed by binary logistic regression and chi-square test. A p-value of &lt; 0.05 was considered statistically significant. Results: Of the 165 patients included, all were female, with a mean age of 50 and majority (97%) with invasive ductal carcinoma (IDC) histology. Baseline characteristics are summarized. 52 had hormone (HR)pos/Her2neg, 51 with triple negative, 47 had HR pos/Her2pos, and 15 had HR neg/Her2pos disease. pCR was seen in 36% of patients. A normal BMI of &lt; 25 (p=0.03), nonsmoker (p=0.01), grade III (p=0.01), HR pos/Her2pos (p=0.02), and HR neg/Her2pos (p=0.0001), were associated with pCR. In patients with triple negative breast cancer, the use of immunotherapy did not influence pCR (p = 0.0565). There were no differences based on age, race, menopausal status, stage, size, presence of LVI or DCIS or multifocal disease. In the 157 patients where Ki-67 was known, tumors with higher Ki-67 values of 30-49% and &gt; 50% achieved pCR compared to those with lower Ki-67 (p = 0.002). Conclusions: Those with normal BMI, non-smokers, and aggressive clinicopathological factors such as Her2 positive, higher Ki67 (30% and above), and grade III disease were more likely to achieve pCR after neoadjuvant systemic therapy. These findings further identify tumor characteristics most likely to respond to neoadjuvant chemotherapy. [Table: see text]
Randomized trial of fixed dose capecitabine compared to standard dose capecitabine in metastatic breast cancer: The X-7/7 trial.
Authors: Qamar J. Khan, Colleen Bohnenkamp, Taylor Monson, Holly E Smith, Milind A. Phadnis, Vinay Raja, Manana Elia, Anne O'Dea, Gregory James Crane, Mark Robert Fesen, Lauren Elizabeth Nye, Maureen Sheehan, Robert E. Pluenneke, Raed Moh'd Taiseer Al-Rajabi, Joaquina Celebre Baranda, Anup Kasi, Richard J. McKittrick, Laura Mitchell, Stephanie LaFaver, Priyanka Sharma
Journal: Journal of Clinical Oncology (2023)

1007 Background: In metastatic breast cancer (MBC), oral capecitabine prescribed at the FDA approved dose of 1250 mg/m 2 twice daily, 14 days on followed by 7 days off, is associated with poor tolerance and high discontinuation rates. Mathematical models suggest a fixed dose, dose dense (7 days on, 7 days off) schedule may be optimal for capecitabine efficacy. We conducted a randomized trial to compare the efficacy and tolerability of fixed-dose capecitabine, 1500 mg twice daily, 7 days on, 7 days off (FD) to the FDA approved dose and schedule (SD). Methods: Females with MBC and any prior lines of endocrine therapy or chemotherapy were included. HER-2 positive patients were allowed with concurrent trastuzumab. Patients were stratified by line of chemotherapy (first or subsequent), measurable disease, and ER status, and randomized 1:1 to either FD or SD. The primary endpoint was 3-month progression free survival (PFS). Additional endpoints included PFS and overall survival (OS). Capecitabine related toxicities were solicited and graded at each visit. Results: Between October 2015 and April 2021, 153 patients were enrolled (N=80 FD, N=73 SD) . 78% were hormone receptor positive/HER-2 negative, 11% each were HER-2 positive and triple negative. The 3-month PFS was 76% in the FD arm and 76% in the SD arm (HR=1.01; 95% CI, 0.52 to 1.94; p=0.99). Landmark analysis of PFS at 12, 24 and 36 months is reported. Non-proportional hazards were detected, so restricted mean survival time (RMST) was used to report estimates of effect. PFS (restricted mean) at 36 months was 13.9 months in the FD arm versus 14.6 months in the SD arm (hazard ratio for progression or death, 1.31; 95% CI, 0.56 to 1.15; p=0.24). OS (restricted mean) at 36 months was 21.2 months in the FD arm versus 19.6 months in the SD arm (hazard ratio for death, 0.80; 95% CI, 0.55 to 1.81; p=0.27). Toxicity related treatment discontinuation occurred in 21 patients (28.8%) in the SD arm compared to 6 patients (7.5%) in the FD arm (p&lt;0.0006). Grade 2-4 toxicities (Table) occurred more frequently in patients receiving SD capecitabine (49.3%) as compared to FD capecitabine (25.0%) (p=0.0018). Conclusions: Fixed dose capecitabine (1500 mg twice daily) on a 7/7 schedule has less toxicity and similar survival when compared to standard BSA-based dosing on a 14/7 schedule in MBC. Clinical trial information: NCT02595320 . [Table: see text]
Changes in time to treatment initiation for patients diagnosed with breast, lung, colon, or rectal cancer during the 2020 COVID-19 pandemic in the US.
Authors: Qinjin Fan, Weichuan Dong, Elizabeth Schafer, Nikita Sandeep Wagle, Jingxuan Zhao, Kewei Sylvia Shi, Xuesong Han, Robin Yabroff, Leticia M. Nogueira
Journal: Journal of Clinical Oncology (2023)

e13516 Background: The COVID-19 pandemic resulted in substantial disruptions in health care and declines in cancer diagnoses in the US. We used nationwide data to examine changes in time to first treatment for patients newly diagnosed with cancer during 2020, the first year of the pandemic. Methods: Adults aged ≥18 years newly diagnosed with breast, non-small cell lung cancer (NSCLC), colon, or rectal cancer between January 2019 and November 2020 were identified from the National Cancer Database. Logistic regression was used to calculate crude and adjusted (by age and sex and diagnosis quarter) odds ratios (AOR) of initiating any treatment within 30 days of the diagnosis comparing 2020 vs. 2019 overall and by quarter. Results: A total of 668,229 adults newly diagnosed with cancer were identified, including 358,255 in 2019 and 309,974 in 2020. Individuals diagnosed in 2020 were more likely to initiate treatment ≤ 30 days of breast (AOR = 1.12, 95% confidence interval [95% CI] =1.11-1.14), NSCLC (AOR = 1.09, 95% CI =1.07-1.11), colon (AOR = 1.13, 95% CI =1.09-1.16) or rectal (AOR = 1.08, 95% CI =1.04-1.12) cancer diagnosis, compared to those diagnosed in 2019. Increases in treatment initiation ≤ 30 days were greatest in the second quarter of 2020 for all four cancers. Findings changed little after adjustment for quarter of diagnosis and AORs remained statistically significant. Conclusions: During 2020, there was an increase in treatment initiation within 30 days from diagnosis, especially in the second quarter. The lower volume of diagnoses and efforts by providers to prioritize cancer care may partly explain the observed improvements. Ongoing evaluation of these changes and cancer outcomes is warranted.[Table: see text]
Association of minimizing the false negative rate of axillary staging surgery in patients with cN1 breast cancer after neoadjuvant chemotherapy with surgical overtreatment.
Authors: Alison Laws, Saskia Leonard, Julie Vincuilla, Tonia Parker, Olga Kantor, Elizabeth A. Mittendorf, Anna Weiss, Tari A. King
Journal: Journal of Clinical Oncology (2023)

587 Background: Efforts to minimize the false negative rate (FNR) of axillary staging in cN1 breast cancer patients (pts) treated with neoadjuvant chemotherapy (NAC) have received much attention since the publication of ACOSOG Z1071. We first adopted sentinel node biopsy (SNB) with a requirement of retrieving ≥3 nodes, and later transitioned to targeted axillary dissection (TAD) with a requirement of retrieving the biopsy-proven clipped node (CN) and ≥3 nodes overall. Group consensus was to perform axillary lymph node dissection (ALND) if these technical requirements were not met. This study evaluates likelihood of surgical overtreatment with ALND due to technical failures of SNB or TAD in cN1 pts who converted to ypN0 status, and reports oncologic outcomes with each approach. Methods: Among 598 cN1 breast cancer pts treated with NAC from 2017-2022 in our prospective institutional database, we included 191 (31.9%) with attempted SNB or TAD and ypN0 status. We used descriptive statistics and chi-squared tests to compare technical complications of SNB vs. TAD resulting in requirement for ALND per group consensus despite ypN0 status. Kaplan Meier methods were used to determine oncologic outcomes in those treated with SNB or TAD alone. Results: Planned axillary surgery was SNB in 77 (40.3%) pts and TAD in 114 (59.7%). The CN was not visualized for seed localization in 14 pts (12.2% of planned TAD) and the seed was not found to be within the CN intra-operatively in 20 pts (20.0% of those with seed placed). Technical failures resulting in requirement of ALND per group consensus criteria occurred in 14 (18.2%) pts with planned SNB and 17 (14.9%) with planned TAD. Among planned TAD pts, the rate of not retrieving the CN did not change over time (p=0.52). Median follow-up in those treated with SNB alone (n=79) was 3.5 years with 1 (1.3%) axillary recurrence as well as 2 local and 2 distant recurrences and 1 non-breast cancer death. 3-yr recurrence-free survival was 90.4% (95%CI: 79.5-95.7%). Median follow-up in those with TAD alone (n=92) was 1.8 years with no recurrences or deaths. Conclusions: This study contributes to a growing body of literature supporting the oncologic safety of omitting ALND in cN1 ypN0 pts treated with NAC, irrespective of the axillary staging approach. Technical limitations in identifying ≥3 nodes or localizing and retrieving CNs resulted in overtreatment with ALND in a significant proportion (≥15%) of ypN0 pts, without significant differences between SNB vs. TAD approaches. These data support consideration of re-evaluating NCCN guidelines recommending retrieval of ≥3 nodes and localization of the CN to minimize risk of overtreatment. [Table: see text]
The overall survival analysis of FUTURE-C-PLUS: Combination of famitinib with camrelizumab plus nab-paclitaxel as first-line treatment for advanced, immunomodulatory triple-negative breast cancer—An open-label, single-arm, phase 2 trial.
Authors: Li Chen, Shao Zhimin, Zhonghua Wang, Wentao Yang, Yizhou Jiang, Songyang Wu, Jiong Wu, Genhong Di, Guangyu Liu, Keda Yu, Lei Fan, Junjie Li, Yifeng Hou, Zhen Hu, Canming Chen, Xiaoyan Huang, Ayong Cao, Xin Hu, Xiaoyu Zhu
Journal: Journal of Clinical Oncology (2023)

1086 Background: Camrelizumab and nab-paclitaxel demonstrated promising anti-tumour activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC) in FUTURE trial. Anti-angiogenic agents have been reported to facilitate immune infiltration. Famitinib is a tyrosine kinase inhibitor targeting VEGFR-2, PDGFR and c-kit. The FUTURE-C-PLUS trial (NCT04129996) which added famitinib to camrelizumab and nab-paclitaxel is a single-arm, phase 2 trial evaluating this novel triplet combinatorial strategy in patients with advanced immunomodulatory TNBC. Study design and the primary endpoint ORR has been reported previously (Zhi-ming Shao, et al. ASCO 2021, Abstract 1007). The final PFS data had been published in Clinical Cancer Research (Clin Cancer Res 2022;28:2807–17). Here, we reported the final overall survival of this trial. Methods: Briefly, this study enrolled women aged 18-70 years, with previously untreated, histologically confirmed, unresectable, locally advanced, recurrent or metastatic immunomodulatory TNBC. Immunomodulatory TNBC was defined as CD8 expression on at least 10% of cells using immunohistochemistry analysis. Eligible patients received the triple therapy. Results: Forty-eight patients were enrolled and treated between Oct 2019 and Oct 2020. The median follow-up was 33.1 months (range, 31.8–34.4). 39 (81.3%, 95% CI 70.2-92.3) patients had a confirmed objective response which has been reported in ASCO 2021. At this updating data cutoff (Feb 1, 2023), the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). While overall survival was 29.4 months (95% CI, 23.3-35.5). The disease control rate was 95.8% (46/48). The most common treatment-related grade 3 or 4 adverse events were neutropenia (16 [33.3%]), anemia (5 [10.4%]), febrile neutropenia (5 [10.4%]), and thrombocytopenia (4 [8.3%]). No new safety concerns were detected. No treatment-related deaths were reported. Conclusions: These data, combined with those from our previous reports, provide further evidence for the triplet combination of famitinib, camrelizumab and nab-paclitaxel as an active therapy in advanced Immunomodulatory TNBC. To our knowledge, this is the best overall survival reached in first-line treatment of advanced TNBC. A randomized controlled FUTURE-Super trial is ongoing to further validate these findings. Clinical trial information: NCT04129996 .